ANG II receptor blockade enhances anti-inflammatory macrophages in anti-glomerular basement membrane glomerulonephritis

Abstract

ϩ macrophages, with a few CD4 ϩ cells infiltrating the glomeruli. Necrotizing and crescentic glomerular lesions developed by day 7 with the increase of proteinuria. AT 1R was expressed on CD8 ϩ and CD4 ϩ cells and on ED1 ϩ macrophages. Low-dose ARB had no anti-inflammatory effects in anti-GBM GN. However, highdose ARB reduced glomerular infiltration of CD8 ϩ cells and ED1 ϩ macrophages and suppressed necrotizing and crescentic lesions by days 5 to 7 (P Ͻ 0.05). In addition, high-dose ARB reduced the numbers of ED3 ϩ -activated macrophages, suppressed glomerular TNF-␣ and IFN-␥ production, and downregulated M1-related chemokine and cytokines (monocyte chemoattractant protein type 1, IL-6, and IL-12). High-dose ARB also enhanced ED2 ϩ M2 macrophages by day 7 with upregulation of glomerular IL-4 and IL-13 and augmented CCL17, IL-1 receptor antagonist, and IL-10. We concluded that high-dose ARB inhibits glomerular inflammation by increasing the numbers of M2 macrophages and upregulation of anti-inflammatory cytokines and by suppressing M1 macrophage development with downregulation of M1-related proinflammatory cytokines.angiotensin II type 1 receptor blocker THE RENIN-ANGIOTENSIN-ALDOSTERONE system (RAAS) is a coordinated hormonal cascade that controls cardiovascular, renal, and adrenal function by regulating body fluid and electrolyte balances as well as arterial pressure (2, 41). ANG II is the principal RAAS effector peptide, and, through its binding to the ANG II type 1 receptor (AT 1 R), ANG II mediates a range of actions, including vasoconstriction, aldosterone and vasopressin release, sodium and water retention, and sympathetic activation. These activities may in turn induce hemodynamic alterations and hypertension. In addition to its systemic hemodynamic effects, ANG II was recently reported to be associated with several pathophysiological actions that facilitate specific tissue and organ injuries, including the production of proinflammatory mediators, cell proliferation, extracellular matrix synthesis, and release of reactive oxygen species (40,42).AT 1 R blockade (ARB) selectively inhibits the binding of ANG II to AT 1 R, and recent evidence indicated a role for ARB

Estradiol Promotes M1-like Macrophage Activation through Cadherin-11 To Aggravate Temporomandibular Joint Inflammation in Rats

“…The number of synovial macrophages is correlated with the clinical disease activity (34,35); selective macrophage depletion has a strong antiinflammatory effect in animal models of arthritis (36,37). Generally, M1 macrophages are proinflammatory, whereas M2 macrophages are anti-inflammatory (15)(16)(17)(18). We not only showed that E2 potentiated accumulation of macrophages (CD68 + ) among the infiltrated mononuclear cells in the synovium of the inflamed TMJs, but also identified that the accumulated macrophages were mainly M1-like macrophages.…”

RETRACTION: Angiotensin II and Canonical Transient Receptor Potential-6 Activation Stimulate Release of a Signal Transducer and Activator of Transcription 3–Activating Factor from Mouse Podocytes

“…For example, there is evidence of marked oxidative stress in nephrotoxic serum models of mouse glomerulonephritis, and in particular marked upregulation of NADPH oxidase and increased generation of superoxide free radicals (Kinoshita et al, 2011). Interestingly, these effects were reduced by AT 1 antagonists, which have long been known to reduce histopathologic changes and proteinuria in this model (Suzuki et al, 1998;Mii et al, 2009;Aki et al, 2010). In addition, there is an increase in glomerular intracapillary pressure in these diseases (Maddox et al, 1975;Brenner, 1978), which may lead to increased mechanical stimulation of podocytes (Endlich and Endlich, 2006).…”

Tumor necrosis factor-α: regulation of renal function and blood pressure

“…The stimuli for their migration to the kidney and TNF-␣ production are likely increased reactive oxygen species and enhanced expression of endothelial adhesion molecules and chemokines by the kidney in response to elevations in renal-derived TNF-␣. Inhibition of AT 1 receptors (7,121) as well as reactive oxygen scavenging (30) reduces renal-derived TNF-␣, proinflammatory cytokine production, and immune cell infiltration and activation. Similarly, ANG II infusion increases leukocyte infiltration and production of inflammatory cytokines, all of which are prevented by blockade of TNF-␣ with etanercept (33,96).…”